David Sinclair on the Brink of Anti-Aging: Reprogramming Cells for Eternal Youth

other thing that's becoming popular is taking lowd do Viagra or sedil it's so funny I can't imagine taking lotos Viagra in order to perform better at a chess tournament for instance this isn't your average business podcast and he's not your average Host this is the James aler show can you see this one James this one here is a recognize those guys uh I don't okay so that here are their signatures uh Francis Crick and Jim Watson okay the founders of DNA or the discoverers of DNA yeah yeah so they're my inspiration every day well it's

interesting because one of the things I want to talk about is a recent paper you published uh I don't actually I don't know how recent it was but inform the information Theory of Aging where we discuss how DNA essentially l L it's a it's an interesting model of Aging you basically discuss how DNA loses information about who we were the moment we were born and that's what basically triggers the aging process and if somehow we could keep that information intact or reprogram the DNA through the epigenetics to if we can keep that information intact we

could reverse aging am I at a 20,000 foot level am I summarizing the paper okay it's very complicated paper yes you did a great job um you're welcome to come work uh in my lab if you want can you give me an honorary PhD I'll do it if you can give me an honorary PhD uh sure I can write you up one I'm not sure Harvard would let me but uh we can have something for you but yeah the um the information Theory of Aging uh has really developed since we last talked was about a

couple of years ago what we were proposing is that the aging process isn't just where and teror we're not just like cars that run out of gas or break down we're more like computers and there's information that we get from our parents um both genetic and epigenetic so genetic is the DNA and the epigenetic is the control of the DNA because of course every cell is different they need to turn the genes on in different ways that's the epig genome um and what I'm proposing is that in the information Theory of Aging or ioa IA

is that it's the of this control system that's the main problem during aging and what happens is over time through various insults to the cells or bad living bad Lifestyles that program that controls the DNA gets lost over time and cells forget how to work they become old dysfunctional and we get diseases and die a coroller of the of the hypothesis that's I think the most exciting is that unlike mutations in DNA which are largely ireverse versible the epigenome is malleable and we believe there's a backup copy of that information in every cell that can

be flipped like a a reset switch to reinstall this epigenetic software in the body and therefore that would be true age reversal and that's your your theory that there's this backup copy and what I mean I guess the idea of DNA is that you know every piece of DNA contains all the information about who you are and so somewhere there's DNA that hasn't been kind of you know lost information so somewhere there's a backup that has all the correct DNA for you that's right uh and and the control systems that's the important thing so some

of the the evidence that this is true or could be correct is that we can clone animals um even monkeys from old cells you take a skin cell from an old monkey uh you can generate a new monkey and that monkey starts out life fresh it's new it's rejuvenated and it goes on to live a normal healthy lifespan that tells us that the information to be young is still in cells and that yes we have mutations there's no question that we lose some of the DNA but largely the information is intact can I ask how

would you be able to tell if it wasn't intact so like let's say you took some skin cells from an old monkey and clone cloned it uh meaning you know put it in an egg and I don't know had some monkey give birth to it I don't know actually what cloning really does but uh how would you know that the information wasn't sort there because the monkey would be born old or what would happen exactly exactly the the the lineage of monkeys that have been cloned would eventually die out because you'd get older and older

uh monkeys and the monkeys would Age prematurely but they don't they live normally so that's that's me says that the information is still there you just need to reset the software and so so there's two things one is basically what are the the habits or Lifestyles that de that increase this information loss on the control so it no longer kind of manages the DNA correctly and we get diseased and and die so what what what are the bad habits and then what are the ways to restore things so that or or can you restore things

so that the control basically reset the cells if they're diseased and we're youthful again yeah well some of my colleagues get upset when I talk about age reversal um in my lab there's no doubt that we can do this we can see that cells and even tissues as complex as the eye can be reset permanently um we can restore blindness in mice and now monkeys hum if we can do that in monkeys why don't we do that already in humans well we'll do it next next year well the regulatory authorities want to see safety first

before you stick a gene therapy into the eye of a human but it looks like we'll be able to do that next year if all goes well but can I ask about that like shouldn't I as a human be allowed to decide about what I want to do with my eyes as opposed to saying oh well the FDA says I'm not allowed to try this yet I'm going to listen to the FDA like like do you listen to the post office worker about how to live your life or do you listen to yourself well yeah

it's I'm I'm I have limit libertarian streaks myself I think that everybody should have a right to do to their body what they want as long as it doesn't hurt someone else um um including uh suicide so as long as you're mentally stable so I I'm I'm with you on that what what Society has evolved to do the way it's engineered now is that unfortunately not everybody is well informed and can be convinced that something is safe and useful by you know who knows who could could be a doctor could be some snake o salesman

and and so those laws there to protect people who don't have enough information or don't have enough education to make those decisions uh some people disagree I I just heard this morning that there's a a group I think it they said it was in uh South America that is establishing uh an area of the planet where you can do more extreme things that are not yet approved by governments uh but I'm not involved in that um you know I've still got my sight set on getting these medicines tested for safety and approved through regular methods

um the other problem James is that the the methods that we have right now to reverse aging like the one I'm talking about for the eye not not anybody can just make this in their garage just making the material for the human trial is costing uh the company $10 million so this is not cheap yet um but I am working on that we're working in my lab on small molecules so chemicals that you could take as a pill uh that could reverse aging we hope or at least uh slow it and uh and do it

for $10 now when that happens um imagine there's you know a drink that you can get at the gas station that re truly rejuvenates you that would be quite an interesting world that that's the one that I'm I'm working on right now that's the Forefront of work in my lab but in the meantime you go ahead Jen well okay so I know for instance we've talked before about um nmn and uh Reser res TR I I don't know how to say it you just said it right yeah and NR which you're not his believer in

but it's interesting i' I the guys at Thorn are big Believers in NR because they figure as a precursor to M nmn uh you know we've talked about all this on other podcast so I won't dive too into it um but there's a various debate about what supplements are anti-aging nmn NR Resveratrol uh uh uh then we also SP spoke about yamanaka factors which seem to be very likely to reduce aging but might have side effects that are dangerous like cancer for instance which would increase aging and uh uh so so I don't know where

you are right now with with all of this research maybe maybe you can give me an update on on that oh yeah sure so the the NR and the nmn story um that debate is I'm not really I'm not in that debate there's a lot of people online who are pumping that up as though it's a controversial um I I'm a Believer in NAD and the precursors of any sort now I I've put a stake in developing medicines based on a whole variety of NAD precursors both natural and synthetic um and have been working to

raise money to make those into medicines for the last 10 years um so I don't I think NR is a very interesting molecule um more studies need to be done so the the controversy just to be clear Is Not What It Seems and I I'm certainly not not out there promoting one thing or another and I don't sell anything uh on the internet just also to be clear if you see if anyone sees my name on a website selling something like NN it's it's not it's not with my permission in fact I spend more money

than I want to each year on legal action to try and curtail that activity really people are trying to sell stuff saying David Sinclair recommends every day there's there's something I get a loaded to it's it's constant yeah w I take I take all of them I take NN well I take NN and I take Thorn's rerel which I guess is Resveratrol um well I do something similar I I still take R veratrol in my yogurt in the morning um a teaspoon and then the Ann um up to a gram of that um and I

I'm still researching it in my lab as well trying to see what the upside downsides are how it works uh we're about to submit a paper that that pinpoints how res virtual works in in the mouse how it's really acting um but yeah I I'm a strong believer in those two molecules um you can think of nmn or NR as the uh as the gas so the gas uh that you fill up the car with the petrol for those in the uh the common well and then the accelerator pedal is the Resveratrol so they they

work together on the enzymes that control aging that I work on called the cin and those cin control the epigenome um and so it's linked as part of this information Theory of Aging and so by taking Resveratrol and nmn um my hope I Haven Prov proven it yet but my hope and belief is that it's activating my seruan defenses turning on those enzymes giving them gas giving the accelerator pedal a push and keeping me younger for longer um what I can tell you so far is it hasn't hurt me I do measure my blood work

every few months um and my blood work looks fine but you know it clearly it's an experiment in progress um I hope one day to uh to perhaps outlive my critics that would be uh a nice thing um that's the best revenge yeah we'll we'll see uh and and there are a fair number of those but really I I'm just uh trying to keep my head down focus on the research and you asked me what's the latest thing cuz the the nmn research that we did we're still doing a bit of it we just are

about to publish not publish a submit a paper showing that NN extends lifespan in in mice um especially female mice and um so that's that's coming most of my research now has has been directed at understanding the software of the body beyond the cerin what else is involved in causing aging to occur and how do you reset that and we had a paper published in cell uh in January last year that showed that or showed evidence that Chang to the epome can drive aging so we made a mouse it took us 13 years to do

this research made a mouse where we could disrupt the epome we did this by creating uh cuts to the DNA when the mice were young as far as we can tell that didn't disrupt the DNA the DNA just got put back together quite easily but the epigenome got disrupted and we know that damage to cells disrupts the epigenome over time and we'll get to this but stopping damage to your cells is is one good good way to slow down aging because slows down epigenetic changes slows down the software corruption um but this paper what it

showed was that we could drive aging forwards uh by disrupting the epigenome and we could also use three of the Amon artifactors there are normally four used but a a particular subset of three was able to safely reverse aging in those mice so so so you disrupted the epigenome by by damaging the DNA and then using three of the yanaka factors which I which I'll ask you to explain again but by using these it it kind of brought the epome back to start again yeah well not fully we we look at um how the genes

are switched on and off and we can measure all of the genes and we can see whether the majority go back to an earlier youthful pattern and we saw that it was highly significant but did they go back to being age zero no and in fact we wouldn't want them to cuz age zero as you said is cancer so the trick for us was we definitely are standing on the shoulders of the great shinya yamanaka who discovered that the four genes uh that four particular genes that are normally turned on by embryos if you put

them into adult cells in the dish they become stem cells going back to age zero but you don't want to do that because that's a cancer cell so the trick for us was to find a combination of those genes that was safe and even though theoretically we might be causing cancer that's a a a concern but in practice we have not seen any negative effects in our treatments in mice or in monkeys so far which bodess well um we still need to do more work but using three instead of four seems to be the magic

recipe why three instead of four like how did you find out which three did you com did you try all combinations and and why does bringing back the age of a cell to zero cause cancer both excellent questions um so the first is we we tried for two years and by we I mean my students um Wan changlu was the student who deserves the credit and he almost quit because it was so hard and he he kept causing cancer cells instead of reversing aging um well why did he almost quit like was he did he

come into your office crying and is that Dr Sinclair I'm gonna quit uh it was uh it was David and it was yeah he was pretty weepy he was resigned to failure and you know Harvard students set a high bar for themselves and after two years of failure it's pretty tough you know these are students that have never failed a test in their life and my job these days is mainly to just make sure they don't quit and so I said to Wang um look I I've got a really good feeling you got to trust

me I've been doing this for 25 30 years now I've got a good feeling let let's keep going let's do a killer a really good experiment and see what happens and his suggestion was to leave out one of the amaka factors that is known to cause cancer it's called Mick myc um and in retrospect it's it's obvious right you leave out the gene that is causing problems uh but we hadn't tried that yet cuz we thought and most people thought Dogma was that you need it but we thought let's just leave it out and see

if it still works and what happened was his cells went back in age but stopped at about 75% return and didn't go back 100% to age zero and what happens when cells hit zero is they become a stem cell and stem cells grow wildly they don't know how to differentiate and become a tissue um unless you C them and when you do that in animals you get what are called teratomas which are horrible masses of cells and it kills the animal so we don't want to make cells zero because they'll just keep growing so so

when someone gets a stem cell transplant let's say a leukemia patient needs has gone through chemo successfully now needs a stem cell transplant to really get rid of the uh leukemia are they getting cells like that that are age zero or are they aged a little bit those stem cells they're aged a bit they're they're they're not pure stem cells they're not plur potent stem cells injected as far as I know that nobody's doing that that would be dangerous they they differentiate them they turn them into a cell type and then they put them back

in so that the cells don't have runaway growth I see they take the stem cells and they maybe maybe make them a blood cell stem cell and so now they can replace blood as opposed to just being the so the epigenome doesn't tell the new stem cells look new guy you're the new guys on uh in the camp here's what you do the epome is not strong enough to take plop poent stem cells and tell them what to do it is but it needs the right signals and if the cells aren't in the right niche

in the right part of the body they don't get the chemical signals and then they just grow in absence of any control factors uh but if you implant stem cells into the right part of the body let's say the lining of the gut or into the brain they will get the right signals and they they may even trigger epigenetic uh control systems that are that are okay but if you inject it inject stem cells into your blood uh they can just keep growing and you you'll die from uh from that but the ortum is very

very powerful it's it's been neglected for a long time because we didn't have the tools to study it we could read DNA but we couldn't read the epigenetic code that's laid on top but we finally have those tools now and uh what we're realizing is the epigenome is King you know and this might be too much in the weeds for my listeners but I'm really curious where is the epigenome like we know that every cell's got DNA and RNA and all this stuff what's where's the there's now there's this third thing I learned the two

things when I was in elementary school but I didn't know about the epigenome yeah it's it's like where is the Matrix uh what is the Matrix um the epigenome are the control systems that tell Gene a to be switched on and Gene B is Switched Off and the way the cell does that in a simplistic sense is it wraps up the D DNA or Loops it out in a in a in a loop that's accessible to the cell and the Machinery of the cell the proteins and so what the DNA isn't just a a flailing

strand of a long chemical 6 foot long in a Cell It's actually mostly bundled up with little Loops where the genes can be accessed but most of it's bundled up tightly so it cannot be accessed that system is called the epigenome and it changes depending on how you live and how old you are and how how much stress and biological accidents happen but most of when you're born basically you've got these beautiful patterns of bundles and Loops of DNA that's the epig genome now what was tricky was to first of all show that those loops

and bundles become untangled and that's causing aging that was this paper I was telling you about that's what we think is going on and then the next challenge was how do you take that DNA strand that's now lost that pattern of bundles and loops and might now be all mostly loops and now the cell's just reading the wrong gen how do you possibly get those structures to go back to where they came and that was why it was it was almost ludicrous to suggest that it was possible even today I get criticized from colleagues saying

age reversal how can that be possible well what we're looking for in my lab are is information that tells the cell which genes to bundle up again that have become opened up over time and that is going to be the source s of the uh the backup copy um exactly how that is arrange you might say well what is what is that what is the the information that tells the cell how to be young again I don't know what it is I just can tell you I know that it's there because we can tap into

it with our experiments using the Yon artifactors and some chemicals now so so the Y artifactors are they like an epigenome to the epigenome like like they cuz they were there at in the embryo right and they they were basically telling the initial cells hey this is how you be a human and and are you suggesting that okay if we get some these three yam three out of the four yamac factors that essentially act like those initial stem cells that tell us how to be human how to build an epigenome is that what's happening well

we we think the process is different than what yamanaka did it's related but it's different in that what yaka did was to erase the identity of the cells basically strip all those bundles and loops and start again that that we're not doing we're actually doing the opposite we're we're telling the cell how to remember how to behave not losing its complete memory and identity and you know if I draw it if you're just listening what I'm drawing is a an inverted U shape there's an Optimum that we're trying to reach where the cells go back

in time remember their identity and the higher it is the better identity they have and better function if we go too far then you lose it again and that was what yamanaka was doing to make his stem cells and you're right that the yamanaka factors of the epigenome to the epigenome they are the trigger that sets forth a Cascade of events that we're now elucidating um that tells other proteins how to go and rearrange those Loops of DNA somehow back to what they were before and it involves enzymes that take chemicals off DNA called methyls

there are enzymes that are involved in putting chemical tags on the packaging proteins called histones it's very complicated Downstream of these three factors and they seem to be the trigger now what's interesting is why would it work in a in an old mouse or an old monkey or even an old human why would this be true why is the system still in existence um you know we don't need to reverse aging right it's why hasn't it been lost to evolutionary time the reason I think it's still exists in US is that um parts of our

body regenerate right if we cut our liver in half take it out it'll grow back to a normal size liver cut the arm off a salamander it'll grow back back um to an to an arm I hypothesize in the information Theory of Aging that this reset of the body through the three y artifactors isn't used normally in nature not to get younger but to regenerate lost body part body parts which we as humans don't really do very well but of I see so because we're all sort of evolved from the same you know cells a

billion years ago there's some part of us that still contains that ability and that might be encoded in the yanaka factors yeah remnants of this Rejuvenation uh rebuild kind of like a a Deadpool kind of system that that is in us but we just don't turn it on whereas other species do but now hopefully we have the tools to turn this on and repair ourselves like we were young again now would would another approach be like if we if we were really excellent at Gene editing like far more than we are now and and we're

getting better and better every year in terms of genomics if we were excellent at Gene editing could we rebuild these DNA loops and not need the yamanaka factors or yeah if we were good enough I I just I prefer to take the approach that biology knows best we've had more than a billion years of evolution and we we tap into what the cells like like to use I think cells are smarter than us this has been My Philosophy my whole career that said theoretically if we knew which genes needed to be reset in each cell

type we could do that it's a extremely difficult engineering problem because even adjacent cells that are microscopic distance apart might behave differently and trying to Target that that system to each different cell is an overwhelmingly complex problem now that doesn't mean that we couldn't say Target nerve cells in the brain specifically to reset some of those but I think a whole body reset currently is is beyond my imagination for engineering um though never say never but these Y manactors what they do when you when you inject them in these these three out of the four

is they in essentially like a disease spread through the the body or the body part where you inject it and and all these bundles that are Lo fritters of DNA now they kind of get this wakeup call hey you used to be a loop better get back there that's right and how that works we don't know we think there are little little flags on the genes that tell the cell this Gene needs to be reset by twofold in a negative direction or another Gene would be five-fold in a positive direction there's some information in there

we're looking for it we have some breakthroughs just last week uh that I can't yet talk about I think we may have found the the information where and how it's stored that tells the cell where to go and what to do and it it's a whole new biology so I'm I'm crossing my fingers for my students that were on the right track what what the Amar factors are they're not that mysterious these are proteins that um engage DNA they find a sequence of letters in DNA they're called transcription factors and they find them they stick

to the DNA and then they they set off uh the activation of other genes so these are genes that regulate other genes that's all they are but they're like a domino those three dominoes get set and then the rest follows um and then the complexity ensues but uh there's got to in in my view there's there's got to be uh a a program in the form of software one-dimensional software just like DNA uh but probably not DNA that records the youthful epigenome and allows the cell to re-engage and create these original structures of folding of

the DNA so the cell can not just behave like it's young but literally be young again so if there was if there were no regulatory regulatory hurdles what would you personally do right now would you inject these three Yaman artifactors into yourself and or would you drink them or like what would you do like what what what do you see as happening let's say after the regulatory hurdles and and let's say all your tests go well what do you see happening yeah um well you know one is hypothetical one is reality the the reality is

that we we put the three genes inside a domesticated virus called an aav and we inject it into the eye and it it infects the nerve cells and reverses the age of the optic nerve in those animals and hopefully people next year and uh and theoretically you could inject it into your vein and have it infect your entire body and uh and that way you could you know see what happens when you reverse aging or turn on these factors in most of your cells that is doable today it' be fairly expensive it' be fairly risky

but it is doable today um would I do it hypothetically probably not um I think we need a bit more uh safety work but I can imagine a day where um and it's not too far away depending on the regulator's opinion where somebody could be flooded with these viruses and what what we've got James which I want to uh mention is from the outset of this study going back to 2017 we we engineered one Chang my student engineered the system to have an onoff switch so that we could turn it off after we after we

finished with it and turn it back on if we needed it again and the way we did it way he did it was uh we just give the antibiotic doxycycl which some people take from malaria we didn't the antibiotic isn't acting as an antibiotic in this context it just acts as an onoff switch for our virus um and so in the future you could be flooded with the virus it's in every cell or almost every cell but you don't turn it on until you need it so let's say you get injured or you start to

get old or you lose your eyesight you hearing um then you take doxycycl for 2 months in theory if it works you get younger you look younger you feel younger your organs function better you stop the antibiotic and you repeat that process every 5 years so so I guess every organ or part of the body ages differently like with eyesight it it it could be your cornea it could be the nerves in the eye it could be the brain cells that regulate Vision with your uh you know stomach and digestion it's another set of cells

would you need but I guess if you're putting the yamanaka factors in each organ specifically it'll know what to do it'll kind of like you know figure out the the C the subculture of that organ you know get acclimated make friends and then do its job accordingly per organ yeah um James I I I love the way you think it's it's deep thinking the answer is yes somehow the Yon Arch factors know how to reset different types of cells we haven't yet seen a cell type that does not respond to the reprogramming and each cell

type is different of course a brain cell is very different in terms of the packaging that it needs compared to a muscle cell um and so yeah there there is a culture within the cell perhaps it's this this uh this system that we're trying to figure out which is this backup copy that is specific to each cell um and so the cell individually they know what they need to go back to and it's perhaps different literally for every cell in the body the pattern that it needs to go back to um and we don't even

know yet how and when that is laid down is it when the baby is born is it when you're teenager is it different for different organs do your liver become set in youth at two and your brain at 20 these are really interesting questions that we we want to address so so what does that determine how much you need to age the stem cells basically for each organ or well so let's say the that the backup copy of Youth is a chemical that gets added to to DNA just hypothetically that might be the method and

so there's an enzyme that puts a chemical on DNA that says this Gene um needs to stay at this level to be young but over time it drifts away it becomes unraveled and now it's causing problems there's a detector of that chemical on the DNA that the Amon archa is are cause to go there and then it uses that chemicals tag to say all right this this Gene even though it's unraveled this little chemical tag says it actually should be bundled so let's bundle it up and that happens 20 2,000 times across the entire genome

allowing the the cell to repackage its DNA early ier um and I'm what I'm saying is maybe these little chemical tags on the DNA get laid down at different times during development um or maybe it's all you know you wake up on your 12th birthday and suddenly you've got all these tags on your body and that's your your reset stage we don't know that uh it's just speculation you know I'm curious about like the brain in particular like the other day so this is a specific example the other day I learned how to SK for

the first time I went skiing for the first time and uh at one point the instructor and I were walking and we passed these little kids and they waved High to the instructor and I said oh did you give lessons to those kids and he said yeah three weeks ago I gave him a couple of lessons and I said what do you mean they're they're they're on the line for the Black Diamond Hill like they're going like I would I'm not going to be able to do that in 3 weeks they're going down the hard

Hill on this mountain just 3 weeks after you're giving the lessons and I watch them and they're just like effortless you know they're not it's almost like they're not using any muscles they're just cruising on down they're going as fast as possible they're they're fearless and I don't believe the example the the the cliche that oh they don't have as far to fall so they're not that worried about falling like they were literally doing it differently because of their brain and mindset then I would do it and what is happening in in there's something in

the aging process but a difference between me and those kids like what has happened to the brain yeah oh well yeah you're right uh the the young brain has uh is very plastic learns very quickly old brains don't we know that the reason I believe uh that happens is you're you're aging due to epigenetic changes so your nerve cells are starting to turn on genes that shouldn't be turned on in the brain so your your nerve cells might be starting to behave a bit like skin cells which is not going to help you learn it's

not going to help you remember things well um and that's why we we did a study in mice where we aged the mice and they be they were hard of learning you could say they had dementia and then we we could reverse the age of the brain In Those Old mice and we could ask the question can they learn like they were young again and the answer is yes they can so I I really think that the inability to learn is just a matter of epigenetic Aging so like and you were able to reverse this

using the the three out of four yamanaka factors it was part of those experiments yeah is there okay and I'm just asking selfishly like I want to reverse the aging in my brain right now I want to learn like when I was a kid again what can I do uh well uh until we have viruses that are safe for uh for injection into uh your your veins which is a while away uh what we're working on are chemicals that will do the same thing so that it could be swallowed or put on the skin or

injected and we published a paper when was it July last year the first proof of concept study that we could find chemical cocktails that reversed the age of cells and uh and restored that epigenome and we've come a long way since then um it's not published yet but we we are down to some really exciting chemicals that uh could theoretically be put into a a drink uh and consumed that May rejuvenate the body improve memory for example uh I think don't get me wrong I'm not going to be putting this into a drink just uh

this year um but I think if the animal studies work out and we do some human studies then that's you know it's a goal worthy of my attention and and I'm not trying to figure out the chemicals just so I could go to the store and and buy these but uh is it like nmn related or is it yamanaka related like what what types of chemicals are yeah so these vitamin D vitamin K uh it's not that simple um there's some there there's Cocktails so there isn't just one answer uh but we're we're at a

point where we now have it down to one chemical that uh can reverse the age um ostensibly reverse the age of cells in the dish can treat human cells make them younger make them grow even if they stop dividing C essent cells and uh barring any safety issues which of course you can't ignore um it could be made available so right now could you go out and buy some of these well I I do know that some people have looked at our publication from July and have started taking those chemicals or surrogates of those um

but they're doctors you need a prescription so it's not that simple you can't just go out and buy it and it's not just a vitamin it's a bit more complicated than that but uh but you know just uh trust that I'm I'm now laser focused on making this come true if it's possible if it's safe um it's not here yet but it will be if I can do anything about it you know when when you last came on to talk about this I did follow a lot of your advice like in terms of intermittent fasting

you know occasional high-intensity exercise of course sleep uh and the the various supplements you take I take uh and how much of these lifestyle factors are sufficient to compare with this chemical cocktail that you're putting together H we haven't put them side by side but I don't think anything that is out there compared to this we don't see The Usual Suspects rapy and NN doing this reset they're they might assist in the process but um these chemicals are in a different League of Their Own um and so I I think this this is probably why

people are skeptical about my use of the term age reversal because they're not seeing the results that I see in my lab um and I we clearly see that aging is reversible um and these these new discoveries are really uh really powerful more powerful than anything I've seen before so reversible in the sense like let's take an extreme example and and this is something we we almost I believe we briefly talked about back in 2020 or 2019 uh a can can a mouse can a female Mouse who has reached menopause reverse menopause we did that

um and by we I mean my team in Australia lindsy wo was the first author uh yeah so we gave them uh old mice um the equivalent age human age of 70 uh 65 maybe uh we gave them manen and it was just a month later that they were able to produce bable eggs and had normal Offspring and that as far as I am aware is the only known or at least it was the first known way to uh reverse what we call Mousa PA so that so that's incredible but that's not what you're talking

about with this new chemical cocktail you're talking about reversing aging with it's different um what worked in the mice was we stabilized their DNA and that's the main problem with infertility and females the eggs trash their chromosome and there was a protein one of the cin that actually was the problem and by raising NAD we could make sure the chromosomes were nicely packaged in the egg um an old egg by the way the chromosomes are all torn apart it's quite terrible there's no way you're going to produce an offspring for one of those but it's

different um it's different this new age reset isn't just for eggs it's it seems to work on every cell type and you don't just go back a little bit seem to go back a lot um you know 50% 75% in age and reset the pattern of what we call gene expression um and what's interesting is it's not just a temporary temporary reset we've co-published a paper recently that when we um essentially cure glaucoma in a mouse and turn off the yamara factors the effect continues right it's not that you need to keep the factors on

it's truly a reset and then the mouse gets old again and then you just can keep resetting we know we can reset the body at least twice um I'm not sure there's actual a limit to it other than in these experiments the mice got old and died but their eyes were beautiful at the end of the experiment um but yeah so it's uh you know I'm looking forward to us getting better at reprogramming the body of mice so we can make them live longer there was a recent study uh that was published not from my

lab but a group that used our system and they gave it to Old mice the they put the yanaka virus into the the vein instead of the eye and those mice were very old and their remaining lifespan was doubled 109% extra life uh wow which you know is a good beginning but I I would love to be able to make a mouse that could live for you know two three times and but the technolog is not really there yet the biggest obstacle is getting the virus into all the cells evenly and viruses like to pile

up in the liver and uh a few other places um and so what people are doing not me but but people who have the skill in viruses they engineering viruses and even other types of delivery vehicles like nanop particles that can evenly spread across the body and deliver genes so so let's say there's someone like you and a lab like yours in China and I'm assuming there must be Labs working in China on similar things maybe I'm wrong maybe I'm not but we you know they have no ethical barriers to what they're trying wouldn't they

already be injecting humans with this and we would start to know what what results they're getting possibly um surprise me though if if some people in South America started doing this um I've heard that people are doing gene therapy on themselves already down there so you know this is not too far from that and and for you like to to prove okay so so first step is you proved oh there's some effect in mice how do you then prove safety in humans like do you have to get humans to to agree to the risks and

get injected with small amounts or what happens yeah uh so that's been my work with the company that I co-founded called life biosciences here in Boston they've been working since 2018 on this and so you do a lot of studies in mice to see what the mice can tolerate you turn it on for the rest of their life see if they get cancer the answer is no you injected in the whole body do they can get cancer the answer is no so far um and then what we did the company did I shouldn't say we

but the company did um studies in monkeys so they they injected the virus and turned it on in the retinas of of monkeys that had poor vision and their Vision improved and there was no issue with the safety seemingly and so they're doing some more of those studies and then with that data our plan is to go to the FDA uh who were we're already talking to so they're aware of our plans um and giving us some advice or at least pointers I don't know if they're allowed to give advice but they definitely give feedback

um about what we need to do for them to approve a human study in the US um and things look good I don't see any obstacle currently why we shouldn't be um asking for volunteers who are blind um as early as um this time next year and they have to be volunteers of course it's a clinical trial but if if you wake up blind which can happen you get a stroke in the back of the eye um you know what have you got got to lose um I if I did if I was blind I

would try it is it is it kind of a not to use the word here but is it a double blind trial in the sense that uh some people will get the um cure and some people will not and and you don't know who is who well the plan is that everybody will get the treatment just at different stages some people will get it early some people will get the antibiotic later and uh so each person can be their own control but yeah we don't currently plan to leave anybody out of this trial and then

and then how long does it take to determine safety do they have to live out their lives and then you know it's safe no I don't think so so you know you're so it's beyond my area of expertise my my understanding though is because there's no current treatment for blindness um and you can't reverse glaucoma currently um the the FDA and Regulators around the world look more favorably on treatments where there's nothing else you can do so my hope actually is that th those studies if they're successful we do another large- scale study and that

would be sufficient for the drug to be approved it's it's really fascinating and then I guess once it's safe I don't know what phase that is Phase One or phase two then you then you start uh see what's the next phase after that so phase one is safety this is different because it's the eye you get the safety and the efficacy uh the results um in the same trial so this is a phase 1/2 study uh so then if all goes well you know fingers crossed what you're left with is a phase three study which

is expanding it into hundreds of patients maybe thousands um to see how safe it is um given that it's a gene therapy probably the number of patients will not be in the thousands or like something like a diabetes trial would um so I think that a phase 3 probably would take one to two years that's typically what they take so if you want to know when is this available on the market to everybody in the US you know we're still a few years away and I always say a few years away and it ends up

being more so uh but we we will see the the what's exciting to me is the eye is a much faster path than than something like diabetes where you need to be testing it for a long time for safety and you have to spend a couple of years testing it before you can even see if it works would the same would the same drug though that works on the eye have off Lael use for diabetes if you inject it in the gut where wherever diabetes happens um well I I'm aware of research that I'm I'm

an author on that that these factors help with blood pressure I'm not aware of it helping with diabetes in a mouse yet we haven't tested that just to address that but um it can it be used off label well I wouldn't condone that right um that said it off label use of drugs is used all the time especially for compassionate use and um you know I'm just wondering though if the if the cocktail is specific for the eye like it's progr for the eye um yeah the the type of virus is better for the eye

than the whole body you'd you'd want to re-engineer it to infect the whole body so specifically we're using what's called an aav number two for the eye in the mouse whole body we use aav9 so probably it's not the best to use the I version well it all sounds very interesting I I am really excited about all the like you wrote the book lifespan what year was it 2019 or 2018 and um we we spoke about that several times and it's a fascinating read about aging and your approach to it you you know your your

approach as aging as a disease rather than just something we should accept and all the different research you summarize and and it's very exciting now to see how five years later where the research has taken you and and I didn't know about any of these advances that that you have and look good luck thank you for spending the time while you're saving civilization and and the human species thank you for spending the time on on the podcast David there was one question I I wanted to ask so so just just back really fast I had

a podcast recently and okay this started off I was speaking um at a men's group there was several hundred men on this men's group and I was speaking about some random thing and suddenly everybody started talking about testosterone I'm 56 years old and people were asking me do you take testosterone everybody was saying you have to take testosterone you have to take testosterone what what's the and and people were saying at an anti-aging thing testosterone for for men and uh we posted this this clip on some social media and a lot of people were arguing

against this there was a whole battle in the comments that I was not involved in because I don't know anything and but what's your stance on testosterone and this has nothing to do with anything you've been talking about but I'm just curious but what what your stance is on this is in terms of aging and and male aging and so on yeah um so I know fed about this one of my good friends and collaborators with the uh the clinical trials actually has done a lot of testosterone studies in humans and uh and so I'm

hearing it really from the horse's mouth here um there's a lot of data and it's dangerous to summarize I will anyway testosterone is is helpful for some things okay build maintaining and building muscle mass yes is that good for Old Men absolutely uh we lose muscle mass all the time does it extend lifespan is it true anti-aging is it slowing down the process the answer there seems to be no so it it's in between it's useful it's helpful during uh aging uh but it's not an anti-aging medicine and then the third thing I want to

add is you know I I work with a lot of people who come to me for advice and um often it's should I take testosterone um I've seen some really good good uh results naturally uh building up testosterone levels working on the larger muscles of the body like your legs and your back um tonat Aly for instance is a is a supplement that's been shown time and time again to raise testosterone and speaking for myself um I naturally raise my own testosterone uh through those means and don't have to take it um what was the

s mentioned oh Tong cat t o n g k a t and then a l i uh to South East Asian plant extract and Jay do you have some kind of Southeast Asian insight into this well yeah because uh this is what we usually take when oh so I'm from Malaysia but tonat Ali is what we usually advise people would take in Southeast Asia that's why I'm like oh I know that name it's very familiar yeah well the other thing that's becoming popular is taking lowd do Viagra or you know um sophy these are um

nitric oxide donor medicines and lowd do seems to be helpful in maintaining um what's called endothelial function your blood vessels Health um and that declines with age and uh it definitely well not definitely but it probably will help your sex life as well the goal though is to keep your blood vessels youthful and uh and flowing and so um I'm currently trying that and uh uh it does seem to give me the seemingly the benefits of exercise without having to exercise a lot um it's just my personal my personal experience I can't say it's a

clinical trial but I did want to mention that because it it I've heard it from many doctors that this is a thing that they're looking into and Advising the patience it's so funny I can't imagine taking lotos Viagra in order to perform better at a chess tournament for instance it could help though uh yeah I'm just trying it out you know I'm like to experiment to see what works and what doesn't but yeah that's something that you know it's got this stigma cuz it's an erectile dysfunction drug but really it was developed to help with

uh blood flow in the beginning and uh my mother was on it actually because she had lung cancer and one lung removed and I remember trying to get Viagra for my mother and getting all these popup ads on my computer for Viagra and I was thinking it's not for me but you know never say never that's funny I really appreciate it I hope we can update it again at some point and yeah thank thanks for coming on uh you're welcome James um yeah I get asked to go on podcast a lot and I typically don't

because I'm focused on the research um obviously I I love what you do people should read your books they're awesome oh I appreciate it thank you appreciate the really great questions that's uh what's special about your podcast thank you [Music]